Microsatellite instability and or loss of heterozygosity in young gastric cancer patients in Italy

Gastric cancers are rarely diagnosed before the age of 40 years and the inc idence reaches a peak during the 7th decade in the general population. A mo lecular mechanism of early tumor onset may be determined by comparing micro satellite instability (MSI), indicative of error-prone mismatch repair, and loss of heterozygosity (LOH) between gastric cancers in patients less than or equal to 40 years of age and those of older ages. Three to 5 chromosoma l loci, where MSI and/or LOH are commonly found in gastric cancers in the g eneral population, were examined in formalin-fixed, paraffin-embedded sampl es from 102 patients less than or equal to 40 years of age using a polymera se chain reaction-based non-radioactive screening method. MSI acid/or LOH a t a minimum of I locus were detected in 11/102 patients, The frequency of M SI and/or LOH at the D11S904 locus was significantly higher than that at th e D2S119, D2S123, D5S409 and IFNA regions. No preferential genetic changes at the D11S904 locus were observed in elderly patients, Among several clini copathological variables, a statistically significant association with MSI and/or LOH was observed only for tumors located at the cardia, compared wit h tumors at the antrum and the corpus. Our findings suggest that a unique m echanism may be involved in increasing the susceptibility of the D11S904 lo cus for either MSI or LOH, especially for cardia tumors in young patients. Early onset of gastric cancers in patients less than or equal to 40 years o f age is associated with genetic changes at preferential chromosomal loci, including D11S904. (C) 1999 Wiley-Liss, Inc.